Human papillomavirus (HPV) infections of the oral cavity or oropharynx cause about 25% of head and neck cancers (mainly oropharyngeal). The number of HPV-positive oropharyngeal cancers is expected to exceed that of cervical cancers by 2020. Given the role of HPV in oropharyngeal cancers, understanding the epidemiology and natural history of oral HPV infections is salient. Currently, however, such data are limited, and have been restricted almost exclusively to genital (alpha) HPV types. Extant studies suggest that oral HPV prevalence in healthy individuals is low, but likely underestimate the true prevalence of HPV infection in the oral cavity due to restriction to alpha HPV types. Recently, beta and gamma HPV types have been detected in the oral cavity of healthy men and HIV-positive men and women, suggesting a broader spectrum of tropism for these HPV genera. To our knowledge, the presence of gamma and beta HPV types has not been investigated in oral cavity samples from healthy women. There are also no data on sexual behavior determinants of gamma or beta infections in the oral cavity. Furthermore, while a hand-to-mouth route for gamma and beta HPV transmission has been postulated, it has never been explored. This proposal addresses the epidemiology of oral gamma and beta HPV infections among 409 healthy women, aged 30 to 50 years old. We propose to make efficient use of stored samples (including oral and fingernail tip samples) to address the following aims: 1) Estimate the prevalence of oral gamma and beta HPV infections; 2) Determine the concordance between oral and fingernail tip samples for detecting gamma and beta HPV types; and 3) Identify health and sexual behavior determinants of oral gamma and beta HPV infections. Our study also has the potential to identify novel oncogenic oral HPV types. The results of this exploratory study could inform the development of larger epidemiologic and natural history studies of gamma and beta HPV infections in the oral cavity, particularly as our knowledge of the role of these genera in oral tumorigenesis advances. Furthermore, our results will further our understanding of HPV tropism, with potential to contribute to our general understanding of HPV-related biology and mechanisms of transmission and infection.